Risk of Neuropsychiatric Adverse Effects of Lipid-Lowering Drugs: A Mendelian Randomization Study.

Background: Recent studies have highlighted the possible risk of neuropsychiatric adverse effects during treatment with lipid-lowering medications. However, there are still controversies that require a novel genetic-based approach to verify whether the impact of lipid-lowering drug treatment results in neuropsychiatric troubles including insomnia, depression, and neuroticism. Thus, we applied Mendelian randomization to assess any potential neuropsychiatric adverse effects of conventional lipid-lowering drugs such as statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and ezetimibe. Methods: A 2-sample Mendelian randomization study was conducted based on summary statistics from genome-wide association studies for lipids, insomnia, depression, and neuroticism. Single-nucleotide polymorphisms located in or near drug target genes of HMGCR, PCSK9, and NPC1L1 were used as proxies for statins, PCSK9 inhibitors, and ezetimibe therapy, respectively. To assess the validity of the genetic risk score, their associations with coronary artery disease were used as a positive control. Results: The Mendelian randomization analysis showed a statistically significant (P <.004) increased risk of depression after correcting for multiple testing with both statins (odds ratio=1.15, 95% CI: 1.04-1.19) and PCSK9 inhibitor treatment (odds ratio =1.19, 95%CI: 1.1-1.29). The risk of neuroticism was slightly reduced with statin therapy (odds ratio=0.9, 95%CI: 0.83-0.97). No significant adverse effects were associated with ezetimibe treatment. As expected, the 3 medications significantly reduced the risk of coronary artery disease. Conclusion: Using a genetic-based approach, this study showed an increased risk of depression during statin and PCSK9 inhibitor therapy while their association with insomnia risk was not significant.

Personality traits and behavioural and psychological symptoms in patients with mild cognitive impairment.

BACKGROUND AND AIMS: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. METHOD: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. RESULTS: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. CONCLUSIONS: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

[Psychoneurological disorders in acute intoxications by psychotropic drugs and their correction using hyperbaric oxygenation].

The paper presents the results of a study of the clinical features of psychoneurological disorders in 178 patients with acute intoxications by various psychotropic drugs. Hyperbaric oxygenation showed positive changes in psychopathological syndromic kinesis. A sanogenetic rationale is provided for the method of choice in treating this category of patients.

Acute neurologic and psychiatric complications associated with cocaine abuse.

This report reviewed 996 emergency room visits and 279 hospital admissions of patients with complications of cocaine abuse seen at the San Francisco General Hospital between 1979 and 1986. In 143 cases, acute neurologic or psychiatric symptoms were the primary complaint, and case-notes provided sufficient detail for analysis. The major neurologic complications included one or more seizures (n = 29), focal neurologic symptoms or signs (12), headache (10), and transient loss of consciousness (six). Psychiatric disturbances included agitation, anxiety, or depression (33), psychosis and paranoia (24), and suicidal ideation (18). The most serious consequences were found in patients with prolonged seizures or strokes, those who jumped out of buildings, and those who attempted suicide by overdosing with other drugs. There was no correlation between the appearance of complications and the reported route of administration, the amount of cocaine used, or prior experience with cocaine. The number of patients who are seeking hospital attention for these or related complaints appears to be rising substantially. Cocaine abuse, regardless of the use pattern, is associated with a variety of potentially severe neurologic and psychiatric complications.

Effect of chronic exposure to acrylonitrile on subjective symptoms.

A cross-sectional study was performed to clarify the relationship between exposure to acrylonitrile (AN) and its effect on subjective symptoms by using a modified Cornell Medical Index (CMI) health questionnaire. The 7 acrylic fiber manufacturing factories surveyed were classified into 3 groups, namely, group L with a mean environmental acrylonitrile concentration of 1.8 ppm, group M with 7.4 ppm, and group H with 14.1 ppm. The total number of workers engaged in acrylic fiber manufacturing processes (acrylonitrile workers) and reference workers analyzed were 504 and 249, respectively. These consisted of 92 acrylonitrile workers and 108 reference workers in group L, 304 and 102 respectively in group M, and 108 and 39 respectively in group H. The mean values for length of exposure to acrylonitrile were 5.6 years in group L, 7.0 years in group M, and 8.6 years in group H. Neurotic status as determined by Fukamachi's criteria and Cornell Medical Index profiles did not show any AN-related differences between AN workers and reference workers in any of the groups. The subjective symptoms with significantly high prevalences in AN workers were "headache", "tongue trouble", "choking lump in throat", "fatigability", "general malaise", "heavy arms", and "heavy sweating". Except for "choking lump in throat" there was no relationship between the prevalence of symptoms and the length or level of exposure to acrylonitrile. These results suggested that long-term exposure to acrylonitrile at levels up to 14.1 ppm did not induce neurotic effects in acrylonitrile workers, but might cause some reversible subjective symptoms.

Long-term exposure to jet fuel: an investigation on occupationally exposed workers with special reference to the nervous system.

In the present study the results of a neurological and neurophysiological health examination of 29 aircraft factory workers chronically exposed to jet fuel vapors are presented. The exposed subjects were classified into a heavily exposed and a less heavily exposed group. The examination included a standardized clinical neurological examination, measurements of the conduction velocities in the peripheral nerves, and threshold determinations of vibratory sensations in the extremities. All 13 persons examined in the heavily exposed group and 7 of the 16 in the less heavily exposed group stated that they had repeatedly experienced acute effects (dizziness, respiratory tract symptoms, heart palpitations, a feeling of pressure on the chest, nausea, headache) of the jet fuel vapors in the inhaled air. A high rate of symptoms indicative of neurasthenia and psychasthenia and symptoms and signs indicative of polyneuropathy was observed both in the heavily exposed group and in the two groups combined in comparison with reference groups. Considering the presented facts concerning (a) the acute effects on repeated occasions, (b) the high rates of symptoms indicative of neurasthenia and psychasthenia and symptoms and signs indicative of polyneuropathy, and (c) the differences in the observations made between the two groups with varying degrees of exposure to jet fuel, the authors interpreted the results as indicative of a possible effect of long-term exposure to jet fuel on the nervous system.

A clinical, neurophysiological and behavioral study of female workers exposed to 1,1,1-trichloroethane.

Twenty-two female subjects working in a factory in which 1,1,1-trichloroethane was the only solvent used were investigated by means of clinical, neurophysiological and psychometric methods so that the neurotoxicity of the solvent could be evaluated. On the basis of the ambient air concentrations of 1,1,1-trichloroethane ranging from 110 to 990 ppm, the workers were divided into three risk groups and compared with a reference group. No significant difference was observed between the exposed and unexposed females with respect to clinical features, maximal motor conduction velocity, conduction velocity of slow fibers, and psychometric data. The most frequent complaints of the workers were of the "neurotic" type with a slightly higher, but not significant, difference in the exposed group. The results obtained favor the absence of a manifest neurotoxic effect of 1,1,1-trichloroethane under the specific work conditions of the investigation; generally unfavorable work conditions seem to have played a prominent role in the genesis of the neurotic complaints. The importance of a global methodological approach in the study of work-related risks, particularly in neurological and psychological surveys, is stressed.

Nutrition and behavior: complex interdisciplinary research.

Nutrition and behavior research presents a particularly challenging field of study for scientists. An overview is provided of research on nutrition and behavior of adequately nourished populations in industrialized countries. Discussions and findings from research presented include: refined carbohydrate consumption, maladaptive behavior, behavior disorders and learning; a history of the 'Feingold diet' and the basis for its controversy; an examination of recent critiques of research on artificial food dyes and hyperkinesis; indications for dietary intervention of hyperactive preschoolers; the role of iron in behavior disorders; effects of sub-clinical vitamin deficiencies on behavior; trace element analysis studies and violent behavior; and, suggested guidelines for further research into this complex and challenging field. Studies cited are from Canada, France, the United Kingdom, and the United States.

[Postmarketing survey on the clinical use of cefotiam].

We performed a survey of clinical experience of cefotiam (CTM: Pansporin) as postmarketing surveillance (PMS), and evaluated the efficacy and safety of CTM in 10,499 cases of data which were collected during the first 2 years after approval. The following results were obtained. The efficacy rate of CTM in the treatment of various infections was 83.2%, which was equal or superior to the clinical results obtained before approval. A total of 472 adverse drug reactions was reported by 10,499 patients (4.50%). The commonest adverse drug reactions was liver function abnormality (230 cases), followed by dermal symptoms (103 cases), gastrointestinal symptoms (53 cases) and renal function abnormality (20 cases) in the order mentioned. All of these adverse drug reactions had already been known for cephem antibiotics, and no remarkable adverse drug reactions specific to CTM was found. The above PMS results indicate the same efficacy of CTM that obtained from premarketing studies. As regards safety, there was no remarkable unexpected adverse drug reaction and their profile was also the same as that found in premarketing studies. Thus, the utility of CTM was confirmed.

[Neurological examinations of workers with chronic exposure to manganese dioxide during the production of piles and batteries]. / Badania neurologiczne pracowników przewlekle narazonych na dzialanie dwutlenku manganu w produkcji ogniw i baterii.

The authors examined 118 workers making piles and batteries under conditions of exposure to toxic action of manganese dioxide dust. Neurological and EEG investigations showed presence of pyramidal tract lesion signs in 16.9% of workers, extrapyramidal syndromes in 6.8%, peripheral nervous system involvement in 13.5% and neurotic complaints in 42.4%. The frequency of neurological manifestations was directly proportional to the duration of work in exposure. The difference in the frequency of neurotic complaints and signs of peripheral and central nervous system damage was statistically significant between the group exposed to manganese dioxide and the control group. EEG investigations were performed in 51 workers and abnormalities were found in 21 cases.

[Functional disorders of the nervous system of female workers in the rubber industry exposed to benzine vapors]. / Zaburzenia czynnosciowe ukladu nerwowego u pracownic przemyslu gumowego narazonych na pary benzyny.

Neurological examinations were carried out in 173 women working in Rubber Industry Plant "Stomil" employed at work posts involving the exposure to petrol vapours. It has been found than in 43.4% of subjects, the functional disorders of nervous system are more prevalent than in women from the control group occupationally unexposed to any neurotoxic substances. The age of the examined women had no significant effect on the occurrence of the above mentioned disorders whereas long period of work affected increasingly the prevalence of functional disorders in women working under conditions of exposure to petrol vapours. Clinical picture was characterized by a number of non-specific symptoms of different degree of intensity and among the ailments--sleep disturbances were often encountered.

[Effect of simultaneous exposure to fluorine and manganese on health status of workers]. / Wplyw jednoczesnego narazenia na fluor i mangan na stan zdrowia narazonych pracowników.

The effect of fluorine and manganese on the health of workers continually exposed to these elements was studied. The concentration of the chemicals did not significantly exceed maximum allowable concentrations only during three hours of work daily. Thirty-six workers directly exposed to fluorine and manganese were examined and compared with the controls. The authors demonstrated that exceeding permissible norms did not cause evident intoxication symptoms even though working in exposure had lasted for many years. However, some changes in the activity of liver indicatory enzymes may be one of the first symptoms of this organ's damage. Frequently occurring ++periodontosis and leukoplakia of the mucous membrane needed careful stomatological prophylaxis .

[Features of the reaction of the rat to intraventricular administration of the cerebrospinal fluid of patients with manic-depressive psychosis]. / Osobennosti reaktsii u krys posle vnutrizheludochkogo vvedeniia tserebrospinal'noi zhidkosti bol'nykh maniakal'no-depressivnym psikhozom.

Following injection of liquor of patients with maniacal-depressive psychosis into the lateral ventriculi of rats brain, the testing of the animals by the method of "emotional resonance" revealed neurosis-like behaviour changes in some of them. It has been shown that the emergence and the character of these disorders are connected with individual features of the rats and do not depend on the phase of psychosis when the liquor was taken. Administration of the liquor of psychically healthy people and intact rats had no analogous effect.

[Analysis of the structure of admissions and the course of hospitalization of drug addicts treated at the I Clinic for Mental Diseases, Medical Academy, in Gdansk 1982-1988]. / Analiza struktury przyjec i przebiegu hospitalizacji toksykomanów leczonych w I Klinice Chorób Psychicznych AM w Gdansku w latach 1982-1988.

The structure of admissions and the course of hospitalization were evaluated in the group of 78 (48 men, 30 women) with diagnosis of psychoactive substance dependence hospitalized in the Ist Clinic of Psychiatry in Gdansk during the period of 1982-88. The mean duration of hospitalization lasted 24 days. The most numerous (59%) group of opioid dependent patients was characterized by the shortest time of hospitalization. The longest duration of the abstinence symptoms was observed in the group of multiple-substance+ dependent patients. 62% of them were taking the drugs during hospitalization. In the group of euphoria + there was a positive correlation between the period of abstinence symptoms and a duration of hospitalization. Half of the patients discontinued hospitalization before the end of therapy. The abstinence symptoms were treated with neuroleptics, clomethiazole and subcomatic insulin.

[Current views on the pathological changes in the nervous system of persons chronically exposed to organic solvents]. / Wspólczesne poglady na zmiany chorobowe w ukladzie nerwowym u osób przewlekle narazonych na dzialanie rozpuszczalników organicznych.

On the basis of a review of the pertinent literature the author discusses pathological changes present in subjects with chronic exposure to organic solvents. The author describes the most frequent symptoms and signs constituting clinical syndromes--neurosis-like, encephalopathic and polyneuropathic. A number of observations of subjects with long-term exposure to benzine and benzene homologues are quoted. Diagnostic investigations of the nervous system are described which are used in cases of suspected chronic poisoning with organic solvents.

[Methods of statistical analysis in the complex evaluation of disorders of the blood levels of free amino acids in alcoholic abstinence syndrome]. / Metody statisticheskogo analiza v kompleksnoi otsenke narushenii v fonde svobodnykh aminokislot krovi pri alkogol'nom abstinentnom sindrome.

A study was made of the formation of the pool of free amino acids in patients with the alcoholic abstinence syndrome (AAS) of varying gravity as well as in the course of detoxication therapy. On admission the patients demonstrated a marked negative relationship between the levels of alpha-aminobutyric acid, serine, cystine, glutamine and the gravity of the AAS. Both mild and grave patterns of the AAS are characterized by the rise of the content of alpha-aminobutyric acid, glycine, valine, phenylalanine, ammonia and by a dramatic decline of the glutamine level. The most informative parameters determined by linear discriminant analysis in the course of detoxication therapy include alpha-aminobutyric acid, lysine, alanine and glutamine. The adequacy of the use of factor analysis for the assessment of the efficacy of a complex of therapeutic measures is discussed.

[Mental disorders during chemotherapy of malignant testicular neoplasms]. / Psikhicheskie narusheniia pri khimioterapii zlokachestvennykh opukholei iaichka.

Mental disorders developed during the chemotherapy of malignant testes tumors are described as related to the patients' personality traits and their psychogenic response to the disease. In 19 patients treated with Platinum-containing drugs, various mental disorders were noted: asthenic, neurotic, psychopath-like ones which were most marked in cycloid-, epileptoid- and schizoid-accentuated personalities, and in the cases with pronounced psychogenic response to the disease and surgery. The latter response could appear as astheno-depressive, anxious-depressive, astheno-neurotic states.

[Mental disorders in workers exposed to chemicals at work]. / Psikhicheskie narusheniia u rabotaiushchikh s khimicheskimi veshchestvami.

The article considers data on boundary psychic disorders in subjects exposed to chemicals of I-II jeopardy classes. Chemical factor appears to increase risk of psychiatric diseases. The authors suggest periodic psychiatric examination of workers engaged into hazardous chemical production for better occupational selection, early diagnosis and treatment of boundary psychic disorders.

[Clinical and functional aspects of adverse effects of toxic substance complexes in firefighters]. / Kliniko-funktsional'naia kharakteristika neblagopriiatnogo deistviia kompleksa toksicheskikh veshchestv na organizm likvidatorov pozhara.

The study covered influence of combined toxic chemicals on fire extinguishers. Acute exposure of respiratory and peripheral nervous systems was demonstrated. Consequences of the exposure were proved to include polyneuropathies, neuroses and other health disorders.

Do antidepressants change personality?--a five-year observational study.

BACKGROUND: Whether antidepressants influence personality is a major clinical and societal issue due to their widespread use. In an observational study, we investigated whether depressive patients' neuroticism and extraversion scores covary with antidepressant pharmacotherapy, and if so, whether this remains significant after accounting for depressive or anxiety symptoms. METHODS: Major depressive disorder patients (N=237) were interviewed at up to four time-points in a five-year prospective longitudinal study. Changes in neuroticism plus extraversion scores were compared with changes in antidepressant pharmacotherapies and depressive plus anxiety symptoms to uncover any covariation between them. Autoregressive path models were used to examine this covariation at the sample level. Within-subject change was estimated using a random-effects latent change model. RESULTS: Significant covariation is present in the change trajectories between personality scores and depressive symptoms; declining depression scores were associated with rising extraversion and declining neuroticism. Although the personality scores of many patients changed significantly over the five-year study, none of these changes were associated with changes in antidepressant pharmacotherapy. LIMITATIONS: The study covered only two dimensions of personality. Single drug-specific analysis could not be done. Antidepressant blood levels were not measured. CONCLUSION: No evidence emerged for significant covariation of antidepressant pharmacotherapy with neuroticism or extraversion scores. By contrast, changes in both personality dimensions were associated with changes in depressive symptoms, those in neuroticism also in anxiety symptoms. If antidepressants influence these personality dimensions, the effect size is likely markedly smaller than that of the disorders for which they are prescribed.